Adenosine-5'-triphosphate-induced sinus tachycardia mediated by prostaglandin synthesis via phospholipase C in the rabbit heart.
Effects of adenosine 5'-triphosphate (ATP) and adenosine on cardiac sinus pacemaker activity were examined in the rabbit heart. Electrocardiograms of hearts were recorded while using the Langendorff perfusion method. Both adenosine and ATP, added to the perfusate, slowed the sinus pacemaker activity in a concentration-dependent manner. But in about 40% of the cases. ATP higher than 300 microM initially accelerated and then slowed the heart. The sinus slowing caused by adenosine and ATP was blocked by theophylline (a P1 receptor antagonist) and disappeared in the hearts pre-treated with islet-activating protein (1AP). In contrast, the ATP-induced sinus acceleration was not affected by either theophylline or IAP. In about 75% of the IAP-treated hearts. ATP persistently accelerated the sinus pacemaker. In the remaining 25% of the hearts, ATP caused junctional tachycardia, which may have masked the ATP-induced sinus acceleration. Apamin specifically blocked the ATP-induced sinus acceleration, suggesting that P2 receptors are involved. Among various adenine nucleotide analogues, the order of potency in inducing tachycardia in IAP-treated hearts is adenosine-5'-[gamma-thio]triphosphate greater than adenylyl imidodiphosphate greater than adenosine 5'-[alpha, beta-methylene]triphosphate = ATP greater than adenosine diphosphate = adenosine 5'-[beta, gamma-methylene]triphosphate. ATP-induced acceleration was partially blocked by indomethacin and aspirin (cyclooxygenase inhibitors), but not by nordihydroguaiaretic acid (a lipoxygenase inhibitor). These results suggest that cyclooxygenase and not lipoxygenase metabolites of arachidonic acid, e.g. prostaglandins, may be involved in the generation of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
Takikawa
R
R
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Kurachi
Y
Y
Mashima
S
S
Sugimoto
T
T
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009355:Neomycin / Q000494:pharmacology; D010477:Perfusion; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000096:biosynthesis* / Q000502:physiology; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D013616:Tachycardia, Sinus / Q000139:chemically induced* / Q000503:physiopathology; D013806:Theophylline / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011453:Prostaglandins; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D001030:Apamin; D000255:Adenosine Triphosphate; D013806:Theophylline; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D009355:Neomycin; D001241:Aspirin; D007213:Indomethacin